Department of Pediatrics, Korea University College of Medicine, Korea University Hospital, Seoul, Korea.
J Korean Med Sci. 2010 Sep;25(9):1296-304. doi: 10.3346/jkms.2010.25.9.1296. Epub 2010 Aug 14.
In the present study, we investigated whether and how the mineralocorticoid receptor antagonist spironolactone affects cardiac growth and development through apoptosis and cell proliferation in the neonatal rat heart. Newborn rat pups were treated with spironolactone (200 mg/kg/d) for 7 days. The cell proliferation was studied by PCNA immunostaining. The treatment with spironolactone decreased proliferating myocytes by 32% (P<0.05), and reduced myocytes apoptosis by 29% (P<0.05). Immunoblot and immunohistochemistry for the expression of p38, p53, clusterin, TGF-beta2, and extracellular signal-regulated kinase were performed. In the spironolactone group, p38, p53, clusterin, and TGF-beta2 protein expression was significantly decreased (P<0.05). These results indicate that aldosterone inhibition in the developing rat heart induces cardiac growth impairment by decreasing proliferation and apoptosis of myocytes.
在本研究中，我们通过研究细胞凋亡和细胞增殖，探讨了醛固酮受体拮抗剂螺内酯是否以及如何影响新生大鼠心脏的生长发育。新生大鼠连续 7 天给予螺内酯（200mg/kg/d）处理。通过 PCNA 免疫染色研究细胞增殖。螺内酯处理使增殖的心肌细胞减少 32%（P<0.05），使心肌细胞凋亡减少 29%（P<0.05）。还进行了 p38、p53、聚集素、TGF-β2 和细胞外信号调节激酶表达的免疫印迹和免疫组化分析。在螺内酯组，p38、p53、聚集素和 TGF-β2 蛋白表达显著降低（P<0.05）。这些结果表明，在发育中的大鼠心脏中抑制醛固酮通过减少心肌细胞的增殖和凋亡来引起心脏生长受损。
